The Program Project theme encompasses both basic and clinical research using a broad spectrum of labeled tracers in the study of normal and pathophysiological conditions which can be followed by metabolic markers, neurotransmitter activity and adaptation, and other biochemical pathways in human and non-human primate brain. An essential correlate of these studies is the test-retest paradigm for establishing the reproducibility (baseline range) of a particular PET measurement in a single subject. Thus the validity of changes brought about in somatosensory, neurophysiological or pharmacologic interventions can be established. The study of binding sites of labeled ethical drugs and their effects on metabolic and neurochemical activity in the brain will be developed. Wherever possible and appropriate, these studies will be used to develop quantitative biochemical models, either to provide data on neurochemical parameters in normal and pathological states or to establish diagnostic criteria for specific disease states. Substance abuse studies will address mechanisms of reward in the brain and adaptation of receptors to repeated stimulation, for example the role dopamine plays including metabolic correlates of the addicting properties of cocaine and alcohol. In schizophrenia, we wish to identify possible physiological trait markers and elaborate underlying malfunctions or defects which bring about the disease. These studies include the acute and chronic consequences of drug perturbation of the dopamine system on LCMRglu and the perturbation of various neurotransmitter systems on the properties of other neurotransmitters. In Alzheimer's Disease, the interrelationships between glucose metabolism, hippocampal atrophy, neuroendocrine changes and cognitive impairment, with a particular focus on cortisol disregulation will be examined. Human brain malignancy will be evaluated in terms of LCGMglu, polyamine metabolism and the imaging of growth factor receptors in tumors and correlated with therapeutic efficacy. Opiate receptor research will include investigation of PCP receptors and mu, delta and kappa sites. Clinical populations such as Alzheimer's patients and drug abusers will be assessed. The core programs are designed to provide the basic support needed to carry out a PET research program. The administration will serve to provide the cohesion necessary to be certain that projects are effectively carried out and that information developed becomes quickly available and applicable to all in the project and the scientific community at large.